The proliferative potential of normal mammalian somatic cells is limited, with the vast majority daughter cells eventually entering either a senescent state or undergoing apoptosis. In rodent cell cultures, the emergence of immortalized cell lineages also occurs at a readily detectable frequency. To evaluate the roles of gene products that modulate higher order chromatin structure in these growth regulatory processes, histone acetyltransferases and deacetylases have been examined. A new deacetylase, hHDA1, was cloned and its cDNA sequence determined. The histone acetyltransferase PCAF was subjected to alanine-scanning point mutagenesis to abolish acetyltransferase activity. Overexpression of acetylase-defective PCAF was shown to extend the proliferative potential of human diploid fibroblasts. In related work, the transcriptional coactivators p300 and CBP were revealed to possess histone acetyltransferase activity.